Abstract
Paraquat (PQ), one of the most widely used herbicides worldwide, causes severe toxic effects in humans and animals. 1-methylhydantoin (MH) is an active ingredient of Ranae Oviductus, which has broad pharmacological activities, e.g., eliminating reactive oxygen species and inhibiting inflammation. This study investigated the effects of MH on lung injury induced by PQ. A PQ poisoning model was established by intragastric infusion of PQ (25 mg/kg), and the control group was simultaneously gavaged with the same dose of saline. The MH group was intraperitoneally injected with 100 mg/kg once per day after intragastric infusion of PQ (25 mg/kg) for five consecutive days. All animals were sacrificed on the sixth day, and the lung tissues were dissected for metabolomics analysis. The lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, TNF-α and malondialdehyde (MDA) content were determined according to the instructions of the detection kit. Compared with that in the control group, the content of LDH, TNF-α and MDA in the lung tissue of the PQ group was significantly higher, and the activity of SOD in the lung tissue was significantly lower (all p<0.05). Compared with that in the control group, the content of LDH, TNF-α and MDA in the MH group was significantly higher, and the activity of SOD was significantly lower (all p<0.05). However, the differences in SOD activity, LDH activity between the PQ and MH groups were not statistically significant (all p > 0.05). There were significant differences in MDA and TNF-α content between the PQ group and MH group (all p<0.05). MH decreased the production of malondialdehyde and TNF-α to protect against the lung injury caused by PQ poisoning, but it had no significant effect on the activity of LDH and SOD. There were significant differences in metabolomics between the MH group and the PQ poisoning group, primarily in bile acid biosynthesis and metabolism of cholesterol, nicotinate, nicotinamide, alanine, aspartate, glutamate, glycine, threonine, serine, phenylalanine and histidine. Therefore, this study highlights that MH has non-invasive mechanisms and may be a promising tool to treat lung injury induced by PQ poisoning.
Highlights
Paraquat (PQ) is a herbicide that is widely used in agriculture and is extremely toxic to humans and animals [1]
BCA protein assay kit and total superoxide dismutase (SOD) activity detection kit was purchased from Beyotime Biological Reagent Co., Ltd. (Shanghai, China), an lactate dehydrogenase (LDH) activity detection kit was purchased from Solarbio Life Science Company (Shanghai, China), and MDH and tumor necrosis factor-α (TNF-α) detection kits were purchased from BestBio Biological Reagent Co., Ltd. (Shanghai, China)
The 30 mice were divided into a control group, PQ poisoning group and MH group
Summary
Paraquat (PQ) is a herbicide that is widely used in agriculture and is extremely toxic to humans and animals [1]. There is no treatment for PQ poisoning, several studies have suggested antioxidant therapy as a viable alternative. Antioxidants such as vitamin C [3] [4] and lysine acetylsalicylate [5] have been shown to be useful in the treatment of PQ toxicity. Metabolomics, often referred to as "metabolic profiling," is the systematic profiling of metabolites and their temporal changes in biofluids or tissues of organisms [6]. Metabolomic profiling of biological systems has the powerful ability to provide biological understanding of the metabolic functional states responding to environmental factors or other perturbations [7]
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